JPH0546900B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to reagent test devices, and more particularly to:
A reagent test device using a substrate material for reagent test devices that prevents or substantially eliminates cross-contamination of reagents and run-over problems that can interfere with quantitation or measurements based on colorimetric changes. Regarding.

BACKGROUND OF THE INVENTION Ever since biochemistry began to emerge as an unexplored field of major science, the technology of analytical chemistry has continued to advance significantly, resulting in the development of better analytical methods and tools for solving various problems. is necessary. Similarly, medical professionals are spurring the development of analytical chemistry with a pressing need to quickly obtain highly accurate results.

In order to meet the demands of not only medical professionals but also other evolving technologies such as brewing and chemical manufacturing,
The so-called “dip-and-read”
Numerous analytical methods, compositions, and instruments have been developed, including (type) reagent test devices. Because reagent test devices are relatively inexpensive, easy to use, and provide rapid results, they have found wide application in many analyses, particularly in the chemical analysis of biological fluids. For example, in medicine, a reagent strip test device is immersed in a sample of body fluid, such as urine or blood, to detect changes such as color changes or changes in the amount of light reflected from or absorbed by the test device. A myriad of physiological functions can be monitored simply by observing detectable responses.

“Immersion reading” for detecting body fluid components
Many dip-and-read test devices are capable of making quantitative or at least semi-quantitative measurements. Therefore, by measuring the reaction after a predetermined period of time, the analytical technician can not only provide a positive indication of the presence of a particular component in the sample, but also estimate how much of that component is present quantitatively. Such test devices provide physicians with a convenient diagnostic tool as well as the ability to measure the extent of disease or physical impairment.

Examples of this type of test device currently in use include CLINISTIX, MULTISTIX, KETOSTIX, N-MULTISTIX, and DIASTIX. DIASTIX, DEXTROSTIX and other trade names, the Ames Division of Miles Laboratories, Inc.
Division of Miles Laboratories, Inc.). This type of test device typically consists of one or more absorbent papers impregnated with a particular reagent or reaction system that exhibits a detectable reaction, such as a color change, in the presence of a particular test sample component or composition. It consists of more than one carrier matrix. Depending on the reaction system combined with the specific matrix, these test devices are capable of detecting the presence of glucose, ketone bodies, bilirubin, urobilinogen, occult blood, nitrites, and other substances. A specific change in color intensity observed within a specific time range after contacting the test device with the sample is indicative of the presence of a particular component and/or its concentration in the sample. Some of these test devices and reagent systems are disclosed in U.S. Pat.
It is described in No. 3814668 etc.

Therefore, reagent test devices typically have two or more reagent-loaded carrier matrices, each reagent-loaded carrier matrix capable of detecting a specific component in a liquid sample. The reagent test device may include, for example, a carrier matrix carrying a reagent responsive to glucose in urine, with another matrix responsive to ketones, such as acetoacetate, spaced apart from, but in close proximity to, the glucose-reactive matrix. can have. Products of this type are sold by the Ames Division of Miles Laboratories, Inc.
Laboratories, Inc. under the trademark KETO-DIASTIX. the Ames Division of Miles Laboratories, Inc.
Another reagent test device marketed by N-MultiStats (N-
MULTISTIX) has eight adjacent reagent-containing matrices that perform analytical measurements of PH, protein, glucose, ketones, bilirubin, occult blood, nitrite and urobilinogen.

Despite the obvious benefits demonstrated by their long-term use, these multi-reagent test devices can result in erroneous information if used incorrectly. These multiple analysis instruments are
Composed of complex chemistries and catalytic systems, each reagent matrix contains a unique reaction system that reacts with its particular analyte. Therefore, if a reagent test device is used incorrectly,
It may occur that chemicals are transported from one carrier matrix to another on a reagent test device by the liquid sample being analyzed. If such a situation occurs, reagents flowing out of one carrier matrix will interfere with reagents in other carrier matrices, producing unreliable results. The reagent test device industry typically provides detailed instructions on how to avoid this difficulty, i.e., instructions for properly handling the reagent test device by sucking up excess fluid, etc. Nevertheless, ignorance or disregard of these instructions may allow reagents to flow (run over) from one matrix to an adjacent matrix. The primary aim of the present invention is to prevent this "runover" problem.

Methods to eliminate runovers have been sought for many years, and the present discovery, which is the culmination of extensive research efforts, provides an effective solution to this problem.

Review of the Prior Art Although the patent literature is replete with descriptions of countless attempts to suppress runovers, great emphasis is placed on two basic concepts.
That is, the concept of adsorption of run-over liquid by an absorbent layer placed under the reagent-bearing layer of a reagent test device, and a hydrophobic barrier in the space between the matrices.
The concept is to provide The former method has achieved some degree of success, but the method based on the latter concept has not yet succeeded.

Among multi-layer reagent test devices, U.S. Patent No.
No. 4,160,008 describes a test device in which a carrier matrix containing a reagent formulation is provided with an adsorbent underlayer separated from the carrier matrix by a sample-impermeable (barrier) layer. Each matrix thus forms the upper layer of a laminated composite in which a barrier layer is disposed between the matrix and an adsorbent base layer, and this composite is fixed to a suitable support such as a plastic substrate. . When the test device is immersed in a liquid sample, the sample that would otherwise flow from one matrix to another is mostly adsorbed from the exposed sides to the lower layer of the latter, but due to the blockade of the complex. A layer separates the adsorbent lower layer and the upper reagent layer.

U.S. Pat. No. 4,301,115 discloses and claims a test device consisting of a base plate member coated with a hydrophobic barrier layer having a plurality of spaced apart matrices applied thereto. Although this method substantially eliminates cross-contamination between adjacent reagent zones of a multi-reagent test device, it requires one extra step of applying a hydrophobic material to the base plate member of the reagent test device. .

There are many useful teachings in the patented art regarding the development and use of barriers and/or barriers between reagent matrices that, at least in theory, do not minimize runover problems. It is possible.

U.S. Pat. No. 3,418,083 discloses indicator-impregnated adsorptive carrier matrices treated with wax, oil, or similar "hydrophobic" agents. states that when a blood sample is placed on the treated reagent test device, only colorless liquid components penetrate the test device, while proteinaceous colored blood components remain on the surface and can be removed from the surface. has been done. Therefore, a small amount of liquid containing the analyte is said to penetrate the reagent matrix pad and prevent color interference.

Yet another prior art patent, U.S. Pat. No. 3,001,915, has reagent impregnation test zones for two or more sample components spaced apart, each test zone separated by a non-adsorbent blocker for other reagent impregnation tests. It describes an absorbent paper reagent test device that is separated from the area.
The barrier is polystyrene, rosin,
It is provided by impregnation with materials such as paraffin, as well as various cellulose esters. According to the above reference, reagent test strips are produced by impregnating portions of a paper pad with a glucose-sensitive reagent system. Once the reagent strip is dry, solutions of two or more blocking agents are applied adjacent to the glucose sensitive reagent material. After further drying, a protein-sensitive reagent system is applied, and this operation is repeated by applying alternating reagent solutions and barrier solutions with intervening drying steps.

However, an earlier patent, U.S. Patent No. 2,129,754
The issue describes impregnating paper with paraffin wax, leaving specific areas unimpregnated, and treating these areas with an indicator system for a specific analyte.

In US Pat. No. 3,006,735, the concept of impregnated barriers between reagent zones of a reagent test device is taken one step further by providing continuous reagent zones responsive to different water hardnesses. Water-repellent materials such as oils, waxes, silicones, and printing varnishes are impregnated between these reagent test areas. Like the above two patents, this cited example is
Both the reagent and the barrier are limited to paper or similar absorbent material that is continuously impregnated along its length.

Similarly, U.S. Pat.
No. 3,127,281 teaches the use of a hydrophobic barrier impregnated into a portion of a reagent test device to isolate one test area from another and prevent contamination.

Another patent that describes the separation of indicator reagent areas through the use of non-adsorbent or hydrophobic materials is US Pat. No. 3,964,871.

Although the above patents represent what is believed to be the most relevant prior art to the present invention, the majority of reagent test device products currently on the market are made from hydrophobic organic plastic materials. It has a reagent-impregnated matrix attached to it. Therefore, N-multistats (N-
The multiple reagent test device, known as MULTISTIX, has eight matrices impregnated with different reagents attached to polystyrene film. Since polystyrene is hydrophobic, the reagent test strip can be said to have hydrophobic gaps between adjacent matrices.

Although prior art descriptions provide a theory for eliminating runovers, the fact remains that this problem still exists. US Patent No.
The solutions disclosed in 4160008 and 4301115 come closest to eliminating this runover problem.

Prior art attempts, such as the use of waxes, oils, silicones, etc., have not reduced runover to a clinically meaningful degree, although modest progress has been made to date. However, this is more than offset by the major drawbacks inherent in such an endeavor. For example, the use of hydrophobic materials only in the interstices of the reagent region presents significant technical problems, especially when compared to current technology for the manufacture of dip-read reagent test devices. In addition to the obvious extra step required by applying the barrier to the gap, some of the hydrophobic material overlaps the reagent area, thereby removing the most critical component of the reagent test device. It may thwart the purpose. Furthermore, none of the prior art materials has a surface suitable for adhesion.

Although the above-mentioned drawbacks are not so great as to preclude the use of the technology, prior art hydrophobic materials lack the degree of hydrophobicity required to prevent runover. They do not have a sufficient contact angle to obtain the necessary hydrophobicity, do not have an adsorbent matrix or a suitable surface for binding the reagents, and the reagents are applied directly onto the substrate surface. .

The present invention substantially eliminates cross-contamination between adjacent reagent zones of a multi-reagent test device matrix. Success in eliminating run-over problems leading to cross-contamination and erroneous quantitation was achieved by using a polyester screen instead of the traditional substrate, ie, Trycite (polystyrene). Unlike Trycite, polyester screens virtually eliminate the transfer of liquid from one reagent matrix to another. Importantly, no changes to traditional manufacturing methods are required to create the improved reagent test device.

SUMMARY OF THE INVENTION It is an object of the present invention to replace the substrate of conventional reagent test devices with a polyester screen material that prevents or substantially eliminates run-over problems in reagent test devices having multiple carrier matrices.

A further object of the invention is to provide a low cost and effective means for eliminating or substantially reducing runovers.

According to the present invention, instead of hydrophobic Trycite as the substrate material, a nominal excess of 80-130
Micron, preferably 80-90 micron hydrophilic polyester screen twill material is used,
A reagent matrix is affixed to the substrate using a double-sided adhesive in a conventional manner to form a shape substantially equivalent to reagent test devices currently in use.

The nominal filter rating is the particle size in microns that a filter is capable of passing particles smaller than that value. For example, a filter with a nominal filtration rating of 86 means that particles with a size less than 86 microns will freely pass through.

DESCRIPTION OF THE PREFERRED EMBODIMENTS According to the present invention, the reagent test device replaces the conventionally used Trysite substrate with a nominal tolerance of 80-130 microns, preferably 80-90 microns.
It is manufactured in a conventional manner, except that micron hydrophilic polyester screen twill material is used.

The preferred hydrophilic polyester screen twill material is polyethylene terephthalate which is typically twilled using yarns all of the same diameter, with a greater number of yarns in the warp direction than in the weft direction. In both directions, pass the threads through the top three and the bottom one so that the oblique text appears. The next preferred screen weave is a twill square weave in which each weft thread passes through two warp threads above and one below, creating square holes in a diagonal pattern.

Particularly preferred is polyester fiber PE1020K-86 manufactured by Tetko Inc. of Elmsford, New York. This polyester fiber has a specific gravity of 1.36 and a melting point (both dry and wet) of 15 to 30°. The resulting twill weft has a nominal excess of 86 microns and a mesh count per inch of 165 (weft)/38 (weft).

The polyester screen material according to the invention has the characteristics of low cost and ease of use, resistance to chemical attack and good stability.

The reagent ribbon or matrix material attached to the polyester screen may be formed from any suitable material.
U.S. Pat. No. 3,846,247 teaches the use of felt, porous ceramic materials, and woven or matted glass fibers. Additionally, US Pat. No. 3,552,928 teaches the use of wood materials, cloth, sponge materials, and viscous materials. The use of synthetic resin fleeces as well as glass fiber felts as carrier matrices has been proposed in British Patent No. 1369139. Another British Patent No. 1349623 proposes the use of a light-transparent mesh made of thin filaments as a cover for a paper base matrix. Polyimide fibers are described in French Patent No. 2170397. However, despite these proposals, it is water-absorbent papers such as paper that are primarily used as carrier matrices in the art and are particularly useful in the present invention.

The reagent ribbon or matrix material can be prepared using any suitable method, such as the 3M
They typically contain reagent(s) prior to being applied to the substrate using a double-sided adhesive tape such as Double Stick, available from the Company. A card-like substrate material with glued reagent ribbons is cut transversely according to the prior art, with one end having several 0.5 cm square carrier matrices, and the other end of the substrate being used to hold a reagent test device. Form a reagent test tool measuring 8 cm x 0.5 cm that will serve as a hand.

The following examples compare test devices made in accordance with the present invention with conventional test devices as well as other test devices and illustrate the utility of the present invention. Reagent test matrices for measuring urobilinogen and nitrite were used in this example because they have traditionally caused the worst run-over problems for reagent test devices.

Example 1 To demonstrate the effectiveness of the present invention, a conventional Trycite substrate was applied with alternating reagent matrix areas in a conventional manner using 3M double-sided adhesive tape. A control reagent test piece was prepared. The alternating reagent matrix areas consisted of paper impregnated with reagents specific for the detection of urobilinogen as well as nitrite. Traditionally, this two-component test has had the worst run-over problems for test devices.

A test means for urobilinogen was published in U.S. Patent No.
Manufactured according to Examples 1 and 2 of No. 4158546.

A nitrite-sensitive composition was prepared from the following ingredients: Gantrex AN139 (5 g),
Methanol (250ml), pea-arsanilic acid (1.3g) and sodium lauryl sulfate (2.5g)
g).

These ingredients were dissolved in 250 ml of distilled water in the order shown above, making sure each ingredient was completely dissolved before adding the next ingredient. After dissolution was complete, the solution became slightly cloudy and colorless. Test means were prepared by impregnating paper with the resulting solution in a manner similar to the test means for urobilinogen.

Between each test means of urobilinogen and nitrous acid alternately present on the control test device obtained,
A gap of 0.08 inch was present. Each test device is
There were a total of four urobilinogen test means and four nitrite test means.

For the purpose of manufacturing test devices in accordance with the present invention, a Tetko polyethylene terephthalate twill screen (PE1020K-86) with a nominal excess of 86 microns was used in place of the Trycite and the above-mentioned test device was used as a control test device. The same urobilinogen and nitrite test procedures were applied to polyester screen material.

The resulting control test devices and polyester screen test devices were each immersed in urine, held horizontally, and observed after three minutes for runover or other evidence of cross-contamination. The control test device showed a runover of 55%, whereas the test device made according to the invention showed a runover of 0%.

Example 2 Polyethylene terephthalate twill screen structure (Tetko PE1005K) with a nominal excess of 120 microns
A screen fiber reagent test device was prepared by repeating the procedure of Example 1, except that -120) was used as the screen fiber. The runover amounted to only 0.02% and was determined to be almost non-existent.

Example 3 When repeating the procedure of Example 1 using a polyethylene terephthalate (polyester) twill screen structure (Tetko PE1051K-55) with a nominal tolerance of 55 microns, the runover was 60%.

Example 4 Nominal excess 36 instead of polyester screen
When the procedure of Example 1 was carried out using a micron polypropylene twill screen structure (Tetko PP1050K-36), runover reached 50%.

From the above facts it can be seen that the present invention is suitable for achieving all the objects and objectives mentioned above, which are obvious and also together with the advantages peculiar to the method. The present invention has the advantages of convenience, simplicity, relative low cost, clarity, effectiveness, durability, accuracy, and directness of operation. The present invention substantially overcomes the long-felt and continuing problem of run-over with multi-reagent test devices. The present invention provides a highly effective, simple and inexpensive method for eliminating or substantially reducing runover problems. Test devices made in accordance with the present invention eliminate bridging of liquids between test matrices on the test device and thus eliminate transfer of liquid from one test matrix to another. In addition, the present invention can be effectively utilized in combination with conventional reagent test device manufacturing techniques or manufacturing methods. There is no need for extra layers in the reagent test device to suppress runover problems.
If desired, the present invention can be used with other techniques that have been shown to be effective in suppressing runover problems. Thus, the present invention can be used in conjunction with approaches in the prior art that rely on the use of hydrophobic barrier layers applied to reagent test devices.

Obviously, many other modifications and variations of the invention can be made without departing from the spirit and scope of the invention as previously described.

Claims (1)

[Scope of Claims] 1. A reagent test device comprising a plurality of reagent carrier matrices affixed in spaced relation to one side of a substrate, wherein the substrate has a nominal filtration rate of 80 to 130 microns. A reagent test device characterized by being made of polyester screen material. 2. The test device according to claim 1, wherein the substrate has a nominal filtration rate of 80 to 90 microns. 3. The test device according to claim 2, wherein the substrate has a nominal filtration rate of 86 microns. 4. The test device according to claim 1, wherein the substrate is a screen material made of polyethylene terephthalate. 5. The test device according to claim 1 or 4, wherein the screen material is a twill weave. 6. The test device according to any one of claims 1 to 5, wherein the carrier matrix is made of filter paper.